tbuckley/cabot-search huggingface dataset:
Phase II study of cobolimab in combination with dostarlimab for the treatment of advanced hepatocellular carcinoma.
Authors: Jared David Acoba, Young Rho, Erin Fukaya
Journal: Journal of Clinical Oncology (2023)

580 Background: Immunotherapy is the backbone of hepatocellular cancer (HCC) systemic treatments. Preclinical studies have shown that the combination of anti-TIM-3 antibody and anti-PD-1 antibody is more effective than either therapy alone. Early clinical experience shows that the combination of cobolimab (anti-TIM-3) and dostarlimab (anti-PD-1) can be safely administered. Herein we report an interim update to this phase II, single arm study of cobolimab and dostarlimab in patients with untreated advanced HCC. We hypothesize that this combination immune checkpoint inhibitor therapy will increase the overall response rate (ORR) of patients from 20% (historical control) to 35%. Methods: In total, 42 patients with histologically confirmed, Barcelona Clinic Liver cancer (BCLC) stage B or C HCC will be enrolled on to this trial. Patients receive cobolimab 300 mg and dostarlimab 500 mg on day 1 of each 21-day cycle for up to two years or until disease progression, unacceptable toxicity, or patient withdrawal. CT or MRI is performed every 9 weeks to assess clinical response. The primary objective is to assess ORR. Results: At the cutoff date of September 1, 2022, 16 patients had been enrolled and received at least one dose of cobolimab and dostarlimab. The median age was 68 years (range 44 – 84); most were male (n=15); 5 were White, 5 Native Hawaiian, 4 Asian, and 2 other races. 3 patients had stage BCLC B and 13 had stage BCLC C disease; 1 had Hep B and 5 had Hep C; and 14 were Child Pugh A and 2 Child Pugh B. This interim analysis for efficacy includes 13 patients who had at least one post-baseline tumor assessment (or clinical progression or died). Complete response was seen in 1 patient, partial response in 5 patients (ORR 46%), stable disease in 3 patients (23%), and disease progression in 4 patients (31%). Of the 7 patients with an elevated AFP at baseline, 4 (57%) had a decrease in AFP level by greater than 50%. There was one grade 4 treatment-related adverse event (AE) of neutropenia. Grade 1/2 AEs included pruritus, rash, fatigue, hypothyroidism, and elevated AST and ALT. Conclusions: Interim results indicate that the combination of cobolimab and dostarlimab has acceptable safety with encouraging clinical activity as first line treatment in patient with advanced HCC. To our knowledge, this is the first report of clinically meaningful efficacy of a TIM-3 antibody in combination with a PD-1 antibody in patients with HCC. Clinical trial information: NCT03680508 .
Malignant portal vein tumor thrombosis (PVTT) in patients with hepatocellular (HCC) carcinoma: Insights from a Western single-institutional cohort.
Authors: Sindhu Vikash, Fernand Bteich, Julie Jiang, Devaraju Kanmaniraja, Ana Acuna-Villaorduna, Yvonne M. Saenger, Sanjay Goel, Andreas Kaubisch
Journal: Journal of Clinical Oncology (2023)

552 Background: Macrovascular tumor invasion in the portal vein system is associated with poor survival and response to therapy. The Japanese portal vein invasion (Vp) classification is based on anatomical location of the thrombus and has been reported to predict prognosis in Asian cohorts of patients. Systemic treatment (ST) options have been increasing over the last decade, coupled with a refinement of radiation (RT) delivery and surgical techniques. Modern literature about HCC and PVTT is scarce in the West. Aim of this study was to characterize outcomes of PVTT patients stratified by Vp categories and by treatment strategies in a Western cohort of HCC patients. Methods: A total of 837 patients with HCC, treated at our tertiary referral center between 2010 and 2022, were retrospectively reviewed. 136 (16.3%) patients with PVTT at the time of diagnosis were identified. PVTT was diagnosed by contrast-enhanced computed tomography or magnetic resonance imaging. The extent of portal tumor-in-vein burden was characterized according to the Liver Cancer Study Group of Japan classification. Treatment modalities were delineated. Median OS was calculated for each group. Cox proportional hazard was used to compare OS between groups. Results: Etiology of liver disease was chronic hepatitis B in 18 (13%) patients, chronic hepatitis C in 79 (57%), alcohol in 53 (39%) and NASH in 10 (7%). Our group comprised 8 Vp1, 16 Vp2, 53 Vp3 and 59 Vp4 patients. 42% were in class Child-Pugh A, 42% B and 16% C. 14 (10%) patients underwent surgical resection of their tumor, 31 (23%) received radiation therapy, 90 (68%) were treated with systemic therapy, while 27 (23%) only received best supportive care (BSC). Median OS was 7.2 months in all comers; 16.0, 3.6, and 1.9 months when stratified by Child-Pugh class A, B, C respectively. Patients lived longer when they had more limited PVTT extent (Table). There was a trend towards worse OS in patients with Vp4 tumors compared to more peripheral thrombi (median OS 4.7 vs 12.8 mo, p=0.055). Patients treated with both ST and RT had a better OS than those treated with either alone (median OS 17.7 vs 5.7 mo, p=0.022). Median OS by treatment type is shown in Table. Conclusions: This retrospective study confirms an association between the extent of PVTT and OS in a Western HCC cohort. Patients with adequate hepatic reserve may benefit from more aggressive multi-modality treatment approaches. OS by PVTT extent and treatment modality.[Table: see text]
Attitudes toward prevention options in Lynch syndrome (LS): Comparing frameshift peptide vaccination (FSPVAX), colonoscopy (COLO), and aspirin (ASA) chemoprevention.
Authors: Michael J. Hall, Emma D Riggs, Yana Chertock, Mary Beryl Daly
Journal: Journal of Clinical Oncology (2023)

526 Background: LS is among the most common cancer (CA) syndromes affecting 1:280 individuals and portends high lifetime CA risk. Clinical trials are currently evaluating whether FSPVAX could reduce LS CA risk. FSPVAX enhance immune response to diverse FSP neoantigens in MSI-H tumors and have shown promising results in an MSH2-mutant mouse model and metastatic MSI-H CRC. However, negative public attitudes towards vaccination could undermine this novel therapy. Here, we benchmark attitudes towards FSPVAX for CA prevention against intensive colonoscopy, for which uptake is high in LS, and aspirin chemoprevention, where uptake is generally lower. Methods: The PREVENTLynch survey was distributed electronically to participants in the Fox Chase Cancer Center (FCCC) Risk Registry. LS patients were invited to complete the one-time survey after providing informed consent, and received a gift card incentive upon completion. The study was approved by the FCCC IRB (20-8014). Demographic/personal/familial CA history were collected. Attitudes were measured on 9-point scales indicating low vs high agreement with belief statements: e.g.“Colonoscopy is a convenient way to lower my risk of LS-related CA.” Results: Overall 116 out of 220 invited LS patients completed the survey (response rate 53%). 76% were female, and mean age was 52.7 yrs. 72% had personal history of CA. COLO uptake was high (96%), while ASA uptake for prevention was modest (22%). Side effect concerns were higher for FSPVAX compared to both COLO and ASA (both p&lt;0.001). FSPVAX offered patients significantly less reassurance than COLO (p&lt;0.001) and was significantly less likely to be endorsed/pursued as a treatment (p&lt;0.001). Convenience of FSPVAX was similar to COLO but less than ASA (p&lt;0.001). LS patients with (vs w/o) a personal history of CA(p&lt;0.05) and those &gt;50 yrs old (vs&lt;50)(p&lt;0.05) were more likely to participate in a FSPVAX trial. Conclusions: LS patients’ attitudes towards FSPVAX are mixed. Concerns about side effects and efficacy may limit future uptake similar to ASA. [Table: see text]
Symptom burden and functioning status in patients with advanced upper gastrointestinal cancers.
Authors: Xin Shelley Wang, Lisa M. Hess, Shu-En Shen, Elizabeth Gonzalez, Mona K Jomaa, Astra M. Liepa
Journal: Journal of Clinical Oncology (2023)

311 Background: Providing accurate symptom profiles is essential to facilitate integration of patient-reported outcome measures (PROs) into routine oncologic care. This study described the symptom trajectories and functioning status in patients with advanced esophageal, gastroesophageal junction (GEJ), or gastric cancers. Methods: The study included adult patients with advanced upper gastrointestinal (UGI) cancers who were initiating a new line of therapy at time of enrollment. Multiple symptoms were assessed weekly for 12 weeks, then every two weeks until Week 36 using the electronically administered M.D. Anderson Symptom Inventory GI module (MDASI-GI). Patients also completed the EORTC QLQ-C30 every six weeks. Longitudinal PRO data were analyzed using mixed-effect models. Time to deterioration was estimated using Kaplan-Meier method. Multivariable regression models evaluated the association of PROs with tumor response. Patients were classified in a high symptom burden group if their MDASI-GI symptoms were scored &gt; 4 (scale of 0-10) for trajectory analysis. Results: Of the 111 enrolled patients, primary tumor site was available for 108 patients: esophageal (33%), GEJ (26%), gastric (41%). The mean age was 60.2 years; 70% were male. Nineteen patients who dropped within one week after baseline reported more severe vomiting and inability to eat than those who provided more post-baseline data (n=92). For the 92 patients, the top 6 most severe items at baseline were fatigue, lack of appetite, disturbed sleep, pain, drowsiness, and inability to eat. At baseline, patients who were treatment-naïve (n=43) reported more severe symptom burden and financial difficulty than patients who had received prior therapy (n=49). Those who were treatment-naïve reported faster general activity deterioration during the first 12 weeks than those who had received prior treatment (hazard ratio=2.183, 95% CI: 1.018, 4.673). More severe shortness of breath at baseline was significantly associated with better tumor response by Week 12 (odds ratio=1.35, 95% CI: 1.05, 1.74) for all patients with tumor response data. Trajectory analysis showed high symptom burden for pain (35% of patients), fatigue (60%), disturbed sleep (32%), lack of appetite (60%), drowsiness (54%), difficulty swallowing (37%), and inability to eat (50%) during the initial 12 weeks. High symptom burden continued for pain (41% of patients), fatigue (55%), lack of appetite (59%), drowsiness (48%), and numbness (29%) for Weeks 12-36. Conclusions: This longitudinal study documented high prevalence of disease- and treatment-related symptom burden and functioning deterioration among patients with advanced UGI cancers. These data support the implementation of PRO assessment in the routine patient care of this cohort of patients with significant physical and psychosocial challenges.
Artificial intelligence (AI)-powered immune phenotyping to predict outcomes of immuno-oncology (IO)-based regimens in hepatocellular carcinoma (HCC).
Authors: Hongjae Chon, Chan Kim, Beodeul Kang, Jaekyung Cheon, Gwangil Kim, Chiyoon Oum, Seulki Kim, Gahee Park, Mohammad Mostafavi, Mingu Kang, Chan-Young Ock
Journal: Journal of Clinical Oncology (2023)

601 Background: Anti-PD-(L)1 monotherapy or combination with bevacizumab or ipilimumab are approved treatment options in HCC. Nevertheless, not all patients benefit from IO treatment, and discovery of predictive biomarkers for IO outcome has not been fully investigated. Immune phenotype analysis by AI-powered spatial tumor-infiltrating lymphocyte (TIL) analyzer in H&amp;E whole-slide images (WSI), Lunit SCOPE IO, has shown predictive effect across multiple cancer types. Here, we investigated the correlation between immune phenotype (IP) and the real-world outcomes in HCC. Methods: Real-world dataset of 177 patients with HCC were retrospectively collected from CHA Bundang Medical Center. Inflamed score was defined by the proportion of area with high intra-tumoral TIL density per 0.5 mm2-sized grid. IP status was sub-analyzed by PD-L1 combined positive score (CPS) and prognostic factors including Child-Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage. We evaluated the correlation between IP and IO outcome by regimen (atezolizumab+bevacizumab [Atez+Bev], n=100; nivolumab+/-ipilimumab [Niv+/-Ipi], n=77). Results: The majority of patients (75.3%) were Child-Pugh class A (75.3%) and BCLC stage C (86.5%), respectively. Atez+Bev was mostly received as first-line therapy (92.0%), whereas Niv+/-Ipi as second-line or beyond (98.7%). The inflamed score was significantly higher in patients who had lymph node metastasis ( p=0.008), but it was not correlated with other metastatic sites, or any other prognostic factors. Of 177 patients, 105 (59.3%) patients were classified as having a high inflamed score (≥10%) and 72 (40.7%) patients as having lower than 10%. PD-L1 CPS was significantly higher in the sample with high score compared to those with low inflamed score ( p=0.01387). PFS of Niv+/-Ipi were significantly favorable in the patients with high inflamed score (3-m PFS rate; 44.0% vs 3.61%, 12-m PFS rate; 17.8% vs 0%, Hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.22-0.63, p&lt;0.001), while PFS of Atez+Bev were not different according to inflamed score (3-m PFS rate; 67.5% vs 57.3%, 12-m PFS rate; 36.6% vs 31.0%, HR 0.80, 95% CI 0.48-1.32, p=0.400). Conclusions: Inflamed score, the proportion of area with high intra-tumoral TIL infiltration, can be a clinically significant predictor of PFS of Niv+/-Ipi, but it was not relevant for Atez+Bev treatment outcomes.
IMbrave150: Exploratory analysis to examine the association between bevacizumab (bev) ever being skipped and bev never being skipped in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bev in a global phase 3 study.
Authors: Masatoshi Kudo, Kaoru Tsuchiya, Yu Yun Shao, Richard S. Finn, Peter R. Galle, Michel Ducreux, Ann-Lii Cheng, Tatsuya Yamashita, Hironori Koga, Kenichi Aoki, Kyoko Yamada, Takashi Asakawa, Yuki Nakagawa, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2023)

538 Background: Treatment with atezo + bev has been approved globally for patients with unresectable HCC who have not received prior systemic therapy, based on results from the Phase 3 IMbrave150 study (NCT03434379, Finn NEJM 2020 and Cheng J Hepatol 2022). According to Phase 1b study data (Lee Lancet Oncol 2020), when combined with atezo, bev has a clinically relevant contribution in terms of immune enhancement and normalization of tumor blood vessels. However, it is unknown if bev being skipped due to bev adverse events of special interest (AESIs) has an impact on the efficacy of atezo + bev. Here, we conducted an exploratory efficacy analysis examining patients who had skipped bev vs those who never skipped bev using IMbrave150 study data. Methods: In Arm A of IMbrave150, patients were assigned to receive atezo + bev. Group A-1 included patients whose bev was ever skipped due to bev AESIs. Group A-2 included the patients who were not included in group A-1. Landmark analyses of overall survival (OS) and progression-free survival (PFS) were performed in patients who received atezo + bev for ≥6 months to minimize immortal time bias. Results: Of 210 patients who received ≥6 months of atezo + bev, 69 were assigned to group A-1 and 141 were assigned to group A-2. No obvious differences between groups were observed in the distribution of baseline characteristics. Of the group A-1 patients, 75.4% were BCLC stage C and 76.8% were Child-Pugh A5, while group A-2 patients were 80.1% BCLC stage C and 77.0% were Child-Pugh A5. At the data cutoff (Aug 20, 2020), median OS was 25.8 vs 26.2 months (HR, 1.04; 95% CI: 0.64, 1.69) and median PFS per independent review facility-assessed RECIST 1.1 was 15.5 vs 10.0 months (HR, 1.07; 95% CI: 0.74, 1.55) for groups A-1 and A-2, respectively. Conclusions: The patients who had ever skipped bev did not show different efficacy compared with those who had never skipped bev in this post hoc analysis. Although limitations due to the non-randomized and exploratory nature of this comparison should be acknowledged, the results suggest that skipping bev did not have considerable impact on the efficacy of atezo + bev. Clinical trial information: NCT03434379 .
Cost effectiveness of liquid biopsy for colorectal cancer screening.
Authors: Zainab Aziz, Sophie Wagner, Alice Agyekum, Matthew Prest, Yoanna S Pumpalova, Chin Hur
Journal: Journal of Clinical Oncology (2023)

73 Background: Despite established screening guidelines, adherence to colonoscopy is approximately 60%. Blood-based screening tests, or Liquid Biopsies (LB), have the potential to close this screening gap. Our aim was to determine the cost-effectiveness of LB tests for CRC screening in the US. Methods: We developed a Markov model to compare four CRC screening strategies: no screening, or natural history (NH), colonoscopy (Colo) only, LB only, and colonoscopy to LB hybrid (C-LB). US SEER CRC incidence and mortality data were used to develop and validate the model. Many LB tests are in development awaiting validation; we used the preliminary performance characteristics for CRC screening of 82% sensitivity and 99.5% specificity (base case) from the Galleri multi-cancer early detection test (GRAIL). Screening ran from age 45 to 75; polyp surveillance ended at 85. We assumed 60.6% of the US population would undergo a screening colonoscopy, and 100% adherence for LB. In Colo, nonadherent patients were not offered other screening; in C-LB those who refused colonoscopy underwent LB. Primary outcomes were overall survival, total cost, incremental cost-effectiveness ratio (ICER), number of CRCs, and CRC deaths. Results: In the NH strategy, 5.2% of the population developed CRC and 1.8% died from CRC, with a cost of $7,802.15/individual. Compared to NH, in Colo, 40% of CRCs and 44% of CRC deaths were prevented, at a cost of $10,610.43/individual. In C-LB, 42% of CRCs and 50% of CRC deaths were prevented compared to NH, costing $13,762.61/individual. LB only prevented 2.0% of CRCs and 11% of CRC deaths compared to NH, and cost $34,339.85/individual. While LB showed an incremental benefit of 0.01 life years gained compared to NH, the ICER compared to NH is $2,653,770. Colo was most cost-effective with an ICER of $30,191.04. Although C-LB prevented the greatest number of CRCs, this strategy had an ICER of $457,057.64, above the accepted US willingness to pay threshold of $100,000/life year. We performed sensitivity analysis around base case estimates for LB. At both 70% and 90% test sensitivity, all outcomes remained largely constant. Conclusions: CRC screening with LB alone or with LB in conjunction with colonoscopy among nonadherent patients is not cost-effective in the US context. At this time, LB is unable to detect pre-cancerous colon polyps, which may limit its effectiveness as a CRC screening strategy. [Table: see text]
Circulating tumor cells (CTCs) as liquid biopsies in patients with metastatic colorectal cancer versus other GI malignancies.
Authors: Pashtoon Murtaza Kasi, Walla I Malkawi, Aliasger K Salem
Journal: Journal of Clinical Oncology (2023)

192 Background: Most of the focus on liquid biopsies for patients with colorectal cancers and other solid tumors has been on circulating tumor DNA (ctDNA). Circulating Tumor Cells (CTCs) are the other less talked about liquid biopsies. This is due to need for real-time processing and handling of CTCs, and is less conducive on previously banked samples. We took this prospective discovery endeavor to report in real-time CTC analyses using 2 very different platforms in patients with colorectal and other GI cancers. Methods: CTCs were evaluated using 2 platforms: RareCyte, which is simplistically based on density of CTCs and unbiased selection/identification for enumeration/biomarker analyses, and Parsortix, which is based on size/compressibility of CTCs. All patients signed written informed consent. Up to 4 serial draws were done for each patient (Total = 150 draws; 281 test results). CTCs were identified using standard definitions of nuclear/epithelial markers. À la carte we selected PD-L1, HER2, EGFR, Ki-67, and where adequate, confirmation with panel based single cell sequencing was also performed. Cell cultures were attempted for the Parsortix collections. Results: Patients with colorectal cancer (CRC) had the highest number of CTCs (Mean: 15.8; Median: 7.5). This was in sharp contrast to the number of CTCs in patients with pancreatic cancer (PC) (Mean: 4.2; Median: 3). At least a third of patients with CRC had at least 3 CTCs. Another 17.4% and 11.4% had at least 10, and at least 20 CTCs in CRC; while no patients with PC had more than 20 CTCs. CTCs in clusters were also common at baseline. In addition, we detected a significantly lower number of CTCs from patients receiving treatment versus those were not (Median 2.7 versus 0.7). Striking differences were also observed in CTCs for those with untreated/progressive disease versus those who had responding/stable disease (Median of 2.7 versus 0). Biomarker analyses on HER2/PD-L1/Ki-67/EGFR were feasible when CTCs were detected. There was overall agreement on CTCs detected on either platform. Where available, single cell sequencing data was concordant with clonal aberrations on sequencing. Conclusions: This is one of the largest prospective real-time endeavors in patients with colorectal and other GI cancers providing data on CTCs as liquid biopsies using 2 very different platforms. The descriptive insights gained from processing, enumeration, kinetics, timing of collection, biomarker analysis, costs, comparison across tumor types, attempts at cell culture, and single cell sequencing are of value for studies and investigators considering the use of CTCs in patients with colorectal and other GI cancers. While most of the focus is on ctDNA-based platforms, CTCs offer a different lens from a liquid biopsy standpoint that is complimentary and worth developing further.